Therapeutic Strategies to Target Calcium Dysregulation in Alzheimer's Disease
CELLS
Authors: Calvo-Rodriguez, Maria; Kharitonova, Elizabeth K.; Bacskai, Brian J.
Abstract
Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Unfortunately, none of the current treatments are effective at improving cognitive function in AD patients and, therefore, there is an urgent need for the development of new therapies that target the early cause(s) of AD. Intracellular calcium (Ca2+) regulation is critical for proper cellular and neuronal function. It has been suggested that Ca2+ dyshomeostasis is an upstream factor of many neurodegenerative diseases, including AD. For this reason, chemical agents or small molecules aimed at targeting or correcting this Ca2+ dysregulation might serve as therapeutic strategies to prevent the development of AD. Moreover, neurons are not alone in exhibiting Ca2+ dyshomeostasis, since Ca2+ disruption is observed in other cell types in the brain in AD. In this review, we examine the distinct Ca2+ channels and compartments involved in the disease mechanisms that could be potential targets in AD.
Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report
ANTIOXIDANTS
Authors: Fois, Alessandro G.; Sotgiu, Elisabetta; Scano, Valentina; Negri, Silvia; Mellino, Sabrina; Zinellu, Elisabetta; Pirina, Pietro; Pintus, Gianfranco; Carru, Ciriaco; Mangoni, Arduino A.; Zinellu, Angelo
Abstract
Introduction: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. Methods: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2-related factor 2 (Nrf2), thiobarbituric acid- reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein -SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age- and sex-matched healthy controls. Results: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 +/- 73 mu mol/L vs 880 +/- 212 mu mol/L, p < 0.001) and plasma PSH (4.24 +/- 0.95 mu mol/g prot vs 5.28 +/- 1.35 mu mol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 +/- 0.011 baseline vs 0.025 +/- 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 +/- 70 mu mol/L vs 723 +/- 194 mu mol/L, p = 0.006) and reduced ADMA concentrations (0.501 +/- 0.094 vs. 0.468 +/- 0.071 mu mol/L, p = 0.024). Conclusion: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.
COA
Publication 
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